Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species provide a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. We analyzed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonosis which in nature exhibits both dead-end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer- to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which are also expected to impede onward transmission. All effects were modulated by infection dose. Taken together, these results suggest that as host species become more dissimilar, increased virulence might act as a limiting factor preventing onward transmission. These results can explain observed constraints on rabies virus host shifts, describe a previously unrecognized role of host body temperature, and provide a potential explanation for host shifts being less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission.

进入新宿主物种的病原体是否导致单一感染或继续传播，并可能爆发，取决于指示病例的感染进展。尽管在自然界中很少观察到指数感染，但将病原体接种到新的宿主物种中的实验性接种为荟萃分析提供了丰富且很大程度上未开发的数据源，以识别感染结果变异性的宿主和病原体决定因素。我们分析了 514 种实验性跨物种接种狂犬病病毒的进展，这是一种广泛传播的人畜共患病，在自然界中既表现出死胡同感染，又表现出在新宿主中不同程度的持续传播。来自蝙蝠而非食肉动物的疫苗，从温暖到凉爽的物种引起的感染潜伏期较短，这与病毒排泄减少有关。远亲宿主之间的接种往往会导致更短的临床疾病期，这也有望阻碍继续传播。所有效果均受感染剂量的调节。总之，这些结果表明，随着宿主物种变得更加不同，毒力增加可能成为阻止继续传播的限制因素。这些结果可以解释观察到的对狂犬病病毒宿主转移的限制，描述了以前未被认识的宿主体温作用，并为遗传距离较远的物种之间不太可能发生宿主转移提供了潜在的解释。更普遍，